The pathology of bone marrow failure

Abstract

Leguit R J & van den Tweel J G (2010) Histopathology 57, 655–670 The pathology of bone marrow failure An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerably between childhood and adulthood. In the paediatric age group inherited bone marrow failure syndromes are important causes of bone marrow failure, but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children and adults. We classified the causes of bone marrow failure according to the main presenting haematological abnormality, i.e. anaemia, neutropenia, thrombocytopenia or pancytopenia. The following red cell disorders are discussed: red cell aplasia, sideroblastic anaemia, congenital dyserythropoietic anaemia, haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, iron deficiency anaemia, anaemia of chronic disease and megaloblastic anaemia. The neutropenias occur in the context of Shwachman–Diamond syndrome (SDS), severe congenital neutropenia, cyclic neutropenia, immune‐related neutropenia and non‐immune neutropenia. In addition, the following causes of thrombocytopenia are discussed: congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, immune‐related thrombocytopenia and non‐immune thrombocytopenia. Finally, we pay attention to the following pancytopenic disorders: Fanconi anaemia, dyskeratosis congenita, aplastic anaemia, myelodysplastic syndromes and human immunodeficiency virus (HIV) infection.

Classification of Childhood Aplastic Anemia and Myelodysplastic Syndrome

“…30 In children with congenital amegakaryocytic thrombocytopenia, BM trephine usually has normal absent or low numbers of megakaryocytes but unremarkable erythropoiesis and granulopoiesis at the time of diagnosis. 31 As disease progresses, BM hypocellularity with an RCC pattern develops.…”

Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice

“…If the anemia is caused by transient blood loss or hemolysis, the erythropoietic system, sensitive to reduced oxygen delivery, quickly responds by increasing erythropoietin (EPO) production. Increased EPO levels lead to an increase in erythropoietic activity that results in erythroid expansion in the BM and ultimately a restoration of normal circulating RBC counts (3). In individuals with ineffective erythropoiesis, a defect prevents erythroid cells from proliferating or differentiating normally, leading to abnormal production of mature RBCs and failure to compensate for anemia (4).…”

Myelodysplastic syndrome with myelofibrosis in a 12-year-old patient – A case report

“…The etiologies of cytopenia are different; in pediatric patients, inherited bone marrow failures being major causes of bone marrow failure [14]. In our case, the bone marrow aspirate was normal in contrast with the pancytopenia that led us to the BMB that revealed myelofibrosis associated with MDS.…”